Clinical and laboratory studies are conducted to determine etiology (infection, immunity and/or genetics) for chronic diseases of the peripheral and central nervous system. Current studies include amyotrophic lateral sclerosis, (ALS), polymyositis/dermatomyositis, demyelinating polyneuropathies, Reye's syndrome, multiple sclerosis, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis and myasthenia gravis. Combined clinical data, genetic information, HLA and MLC typing virus serology and virus isolation studies are obtained for these studies. The nature of oligoclonal bands found in the CSF of patients with chronic neurological diseases is under investigation. A neuromuscular disease that occurs in patients who have had poliomyelitis at an early age has been clinically defined; the possibility that this might be due to a late polio virus infection or an abnormal immunoregulation and an immune reaction to neuronal cells is under investigation. IgM monoclonal band has been identified in the spinal fluid of patients with paraproteinemic polyneuropathies and an abnormal blood-CSF and nerve barrier were found. The metabolic activity of the cortex in ALS patients is being studied using the PET scan and 18F 2-deoxy-D-glucose; hypometabolism was demonstrated not only in the motor but also in the paramotor and sensory cortex, suggesting that ALS is a rather generalized process affecting many cortical regions. Patients with bulbar ALS are now studied with Nuclear Magnetic Resonance (NMR) which, from our preliminary findings, appears to demonstrate structural defects in the medulla. Using recombinant DNA alpha2-interferon, an experimental therapeutic trial was conducted in 5 ALS patients. No improvement or beneficial change in the course of the disease was noted. Virological studies were performed in patients with Reye's syndrome and their families and their ability to handle a salicylate challenge was investigated. The effect of aging on the neuromuscular systems is being investigated electrophysiologically and morphologically.